BACKGROUND: Behavioral and socioeconomic factors create considerable obstacles to the elimination of congenital syphilis. A clear understanding of maternal risk factors is important to define interventions in every community. GOAL: The goal of this study was to investigate maternal risk factors for congenital syphilis. STUDY DESIGN: We conducted a case-control and descriptive analysis of 3 groups of live born infants and their mothers consisting of: group I (cases of congenital syphilis), group II (neonates without congenital syphilis whose mothers had been adequately treated for syphilis), and group III (random sample of newborn infants whose mothers have not had syphilis). Data were prospectively collected from personal interview and antenatal records. RESULTS: In the case-control study, including groups I and III, the maternal characteristics independently associated with congenital syphilis in the logistic regression were monthly per capita income under 30 US dollars (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.1-7.4), single status (OR, 2.8; 95% CI, 1.1-7.8), and less than 6 prenatal visits (OR, 3.2; 95% CI, 1.3-8.1). Comparison between groups I and II (only mothers who have had syphilis) showed a strong protective association of prenatal care with congenital syphilis (OR, 0.05; 95% CI, 0.00-0.39). Additional analysis identified 2 separate profiles of maternal characteristics, one consisting of low socioeconomic status and the other of risk behaviors. Some women who had syphilis before or during pregnancy received adequate prenatal care and delivered infants without congenital syphilis. Most of these women had high-risk behaviors but they were, in general, less poor, older, and more educated than mothers of infants with congenital syphilis. CONCLUSIONS: Risk behaviors and low socioeconomic characteristics constituted 2 separate maternal profiles associated with congenital syphilis. Socioeconomic risk factors interfered more with prenatal care. To become more effective, the strategies for prevention of congenital syphilis should be targeted to each maternal profile.